Consumption of NSAIDs and the Development of Congestive Heart Failure in Elderly Patients

Page, John H.; Henry, David

doi:10.1001/archinte.160.6.777

Cited by 435 publications

(247 citation statements)

References 21 publications

(27 reference statements)

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“…Based on this discovery, one might expect that conventional nonselective nonsteroidal antiinflammatory drugs (NSAIDs) other than coxibs should be neutral or even beneficial to the cardiovascular system. However, a significantly increased risk for cardiovascular diseases such as myocardial infarction (MI), hypertension, and heart failure has also been observed to be associated with the administration of the nonaspirin conventional NSAIDs, including but not limited to diclofenac, ibuprofen, naproxen, and indomethacin (8)(9)(10)(11)(12). In addition, there could be rofecoxib-specific events such as the facile formation of a cardiotoxic maleic anhydride derivative from rofecoxib that may contribute to its adverse effects (13).…”

mentioning

confidence: 99%

Metabolic profiling of murine plasma reveals an unexpected biomarker in rofecoxib-mediated cardiovascular events

Liu

Yang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

121

102

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Chronic administration of high levels of selective COX-2 inhibitors (coxibs), particularly rofecoxib, valdecoxib, and parecoxib, increases risk for cardiovascular disease. Understanding the possibly multiple mechanisms underlying these adverse cardiovascular events is critical for evaluating the risks and benefits of coxibs and for development of safer coxibs. The current understanding of these mechanisms is likely incomplete. Using a metabolomics approach, we demonstrate that oral administration of rofecoxib for 3 mo results in a greater than 120-fold higher blood level of 20-hydroxyeicosatetraenoic acid (20-HETE), which correlates with a significantly shorter tail bleeding time in a murine model. We tested the hypothesis that this dramatic increase in 20-HETE is attributable to inhibition of its metabolism and that the shortened bleeding time following rofecoxib administration is attributable, in part, to this increase. The s.c. infusion of 20-HETE shortened the tail bleeding time dramatically. Neither 20-HETE biosynthesis nor cytochrome P4A-like immune reactivity was increased by rofecoxib administration, but 20-HETE production increased in vitro with the addition of coxib. 20-HETE is significantly more potent than its COX-mediated metabolites in shortening clotting time in vitro. Furthermore, 20-HETE but not rofecoxib significantly increases rat platelet aggregation in vitro in a dose-dependent manner. These data suggest 20-HETE as a marker of rofecoxib exposure and that inhibition of 20-HETE's degradation by rofecoxib is a partial explanation for its dramatic increase, the shortened bleeding time, and, possibly, the adverse cardiovascular events associated with rofecoxib. cardiovascular side effect | coxib | eicosanoids | metabolomics | Vioxx

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mentioning

confidence: 99%

Metabolic profiling of murine plasma reveals an unexpected biomarker in rofecoxib-mediated cardiovascular events

Liu

Yang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

121

102

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“…Successful agents include nonsteroidal antiinflammatory drugs (NSAIDs) and intraarticular corticosteroid and hyaluronate injections. Despite the development of cyclooxygenase 2-selective NSAIDs, which can reduce the risk of gastrointestinal bleeding compared with nonselective NSAIDs (1,2), significant concerns remain regarding the systemic toxicities of NSAIDs (3)(4)(5). Intraarticular therapies are, for the most part, devoid of significant systemic toxicity but may have detrimental effects on joint integrity (6,7).…”

mentioning

confidence: 99%

Tidal irrigation as treatment for knee osteoarthritis: A sham-controlled, randomized, double-blinded evaluation

Bradley¹,

Heilman²,

Katz³

et al. 2002

Arthritis & Rheumatism

106

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“…68 Animal models show that rofecoxib interferes with diuretic efficacy, 69 and published case reports suggest that this is also true of celecoxib. 64 In a study of elderly hypertensives, 9.5% of rofecoxib-recipients vs. 4.9% of celecoxib-recipients developed edema, 60 but the significance of this difference is unclear since more celecoxib patients were on concurrent ACE-inhibitor therapy, which may have been protective.…”

Section: Heart Failure Exacerbationsmentioning

confidence: 99%

Review of the selective COX-2 inhibitors celecoxib and rofecoxib: focus on clinical aspects

Loewen

2002

CJEM

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The selective cyclooxygenase-2 (COX-2) inhibitors celecoxib and rofecoxib were designed to have similar efficacy but less gastrointestinal toxicity than traditional nonsteroidal anti-inflammatory drugs (NSAIDs). Their efficacy has been demonstrated in the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, postoperative dental pain and dysmenorrhea. These agents produce fewer endoscopic ulcers, symptomatic ulcers and gastrointestinal bleeds than traditional NSAIDs; although the absolute benefit is small and the gastropreserving effect is negated by concurrent use of low-dose aspirin for cardiovascular risk reduction. Nephrotoxicity and hyptertension remain concerns with COX-2 inhibitors, as they are with traditional NSAIDs. COX-2 inhibitors may be safe alternatives to traditional NSAIDs for patients with aspirin-sensitive asthma. RÉSUMÉLes inhibiteurs sélectifs de la cyclo-oxygénase-2 (COX-2) célécoxib et rofécoxib ont été conçus pour agir de manière aussi efficace que les anti-inflammatoires non stéroïdiens (AINS) traditionnels, mais avec moins de toxicité gastro-intestinale. Ils se sont révélés efficaces dans le traitement de l'arthrose, de l'arthrite rhumatoïde, de la spondylarthrite ankylosante, de la dentalgie post-chirurgicale et de la dysménorrhée. Ces agents provoquent moins d'ulcères endoscopiques, d'ulcères symptomatiques et de saignements gastro-intestinaux que les AINS traditionnels; cependant, le bienfait absolu est faible et l'effet de gastro-préservation est annulé par le recours concomitant à de l'aspirine à faible dose pour la réduction du risque cardiovasculaire. La néphrotoxicité et l'hypertension demeurent une préoccupation avec les inhibiteurs de la COX-2, tout comme avec les AINS traditionnels. Les inhibiteurs de la COX-2 peuvent se révéler une solution de rechange sécuri-taire aux AINS traditionnels chez les patients atteints d'asthme hypersensible à l'aspirine.

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Consumption of NSAIDs and the Development of Congestive Heart Failure in Elderly Patients

Abstract: The burden of illness resulting from NSAID-related CHF may exceed that resulting from gastrointestinal tract damage. NSAIDs should be used with caution in patients with a history of cardiovascular disease.

Cited by 435 publications

References 21 publications

Metabolic profiling of murine plasma reveals an unexpected biomarker in rofecoxib-mediated cardiovascular events

Metabolic profiling of murine plasma reveals an unexpected biomarker in rofecoxib-mediated cardiovascular events

Tidal irrigation as treatment for knee osteoarthritis: A sham-controlled, randomized, double-blinded evaluation

Review of the selective COX-2 inhibitors celecoxib and rofecoxib: focus on clinical aspects

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